Zinc as an essential element plays the crucial role in many physiological, but also pathological processes - zinc controls cell proliferation, differentiation, and viability including the apoptosis. These facts are especially based on the structural role of zinc ions in many proteins including the transcription factors. Due to the role of zinc in many crucial physiological processes, its homeostasis must be intensively controlled. The controlling mechanisms are based especially on the zinc transporters and low-molecular proteins metallothioneins (MTs) of the molecular weight between 6 and 10 kDa, which were firstly discovered in a horse kidneys as the cadmium binding protein. High affinity of metallothioneins to the zinc ions indicates their significant participation in the physiological, but also pathological processes, which are controlled by zinc. This paper summarizes the connection between metallothioneins and zinc and its significance on the molecular basis.